APPLICANT'S ABSTRACT: Cocaine dependence and cocaine+opiate dependence are associated with major psychiatric, medical, and social problems. They have proven difficult to treat. The Substance Abuse Research Center group, an operating unit of the Department of Psychiatry and Behavioral Sciences (University of Texas-Houston Health Science Center),and collaborators in other Departments and Schools of the Texas Medical Center, will further integrate medication development research into their existing program. The expanded center, Substance Abuse Medications Development Research Center, will include work in its three main research environments; treatment research clinic, human laboratories, and preclinical laboratories. Efforts at other sites have been incorporated. The SAMDRC will have collaborating scientists in all essential research environments, with easy access to rich resources in close physical proximity. The diverse resources, high level institutional administrative support, strength of the ongoing work, and demonstrated collaboration among researchers at the site, will assure implementation and completion of all projects. A core and 3 complimentary projects are proposed. The core will provide all essential administrative services, support, common resources, and assure scientific rigor and integrity. The first research project will examine the joint action of medications and setting variables in cocaine dependent patients and patients who are both cocaine and opiate dependent. The second will examine therapy type as a determinant of effectiveness of new medications. The last research project will examine innovative statistical procedures for application to the complex data of drug dependence research and outcome predictors. The theme is examination of the joint action of medications and environmental /setting /therapy conditions. It is well known that medication effects are modulated by diverse factors. These studies, and ongoing work will make substantive contributions in medications development and drug dependence treatment. In addition, the investigators of the Center, collaborating groups, and sites look forward to working with NIDA staff in the development of special projects to examine new medications. The Center will serve as a valuable and unique regional and national research resource.